The impact of maternal allergic sensitization on the development of pre‐ and postnatal immunity

Abstract

Epidemiological studies indicate the importance of pre‐ and postnatal factors in shaping the T‐cell effector response in early childhood. To study the underlying mechanisms we developed a murine model of prenatal sensitization. BALB/c mice were sensitized to Ovalbumin (OVA) before mating followed by OVA‐aerosol‐exposure during pregnancy (BALB/cOVA). The following key results have been recently obtained: (i) free allergen crosses the placental barrier in pregnant mice; (ii) T‐cells from (BALB/cOVA × BALB/c) F1 demonstrated a lowered frequency and reduced level of IFN‐γ production; (iii) F1 mice were challenged with the heterlogous allergen BLG. The antibody response and type I hyperreactivity reaction were accelerated and augmented in these (BALB/cOVA × BALB/c)F1 [=wild‐type phenotype]. This phenotype depends on the maternal adaptive immune system, since (SCIDOVA × BALB/c)F1 showed a normal immune response. The wild‐type phenotype could be reconstituted in (SCIDOVA × BALB/c)F1 by prenatal transfer of CD4 + OVA T‐cells. These data suggest a critical role for maternal T/B cells in shaping prepostnatal maturation of specific immunity to allergens.